[Invasive Mucinous Adenocarcinoma that Invades the Wall of a Cystic Lesion:Report of a Case].

Invasive mucinous adenocarcinoma (IMA) is a rare and special type of lung adenocarcinoma. We report a case of IMA presenting as a cystic lesion in the S10 of the right lung, diagnosed by surgical biopsy and treated with right lower lobectomy. The patient was a 60-year-old man who was found to have a 10-mm-sized frosted ground-glass opacity with a 10-mm-sized air space in the S10 of the right lung while undergoing follow-up after renal cancer surgery in 2018. The air space gradually enlarged and, in 2022, began to show a 40-mm-sized cyst, with partial wall thickening and nodularity on the caudal side. A thoracoscopic partial pneumonectomy was performed to confirm the diagnosis of IMA, and a thoracoscopic radical resection of the right remaining lower lobe was performed. It is important to recognize that adenocarcinoma may occur in patients with thin-wall cavity, as in this case. Additionally, it is necessary to determine the treatment strategy based on the assumption that the tumor may extend to the entire cavity wall, even if it is thin-walled.

Salt loading with unilateral nephrectomy accelerates decline in glomerular filtration rate in the hypertensive, obese, type 2 diabetic SDT fatty rat model of diabetic kidney disease.

For the evaluation of novel therapeutic agents for diabetic kidney disease (DKD), it is desirable to examine their efficacy in animal models by using the glomerular filtration rate (GFR) as an index. For this purpose, animal models that demonstrate a short-term GFR decline because of disease progression are required. Therefore, we aimed to develop such an animal model of DKD by using obese type 2 diabetic spontaneously diabetic Torii (SDT) fatty rats treated with salt loading by drinking water containing sodium chloride with or without unilateral nephrectomy. As a result, we have found that 0.3% salt loading with unilateral nephrectomy or 0.8% salt loading alone caused a rapid GFR decline, hypertension and rapid development of tubulointerstitial fibrosis. Moreover, the addition of losartan to a mixed diet suppressed the GFR decline in SDT fatty rats treated with 0.3% salt loading with unilateral nephrectomy. These results suggest that the model of SDT fatty rats treated with 0.3% salt loading and unilateral nephrectomy could be used as a hypertensive DKD model for evaluating therapeutic agents based on suppression of GFR decline.

Enteropeptidase inhibitor SCO-792 effectively prevents kidney function decline and fibrosis in a rat model of chronic kidney disease.

BACKGROUND: Inhibiting enteropeptidase, a gut serine protease regulating protein digestion, suppresses food intake and ameliorates obesity and diabetes in mice. However, the effects of enteropeptidase inhibition on kidney parameters are largely unknown. Here, we evaluated the chronic effects of an enteropeptidase inhibitor, SCO-792, on kidney function, albuminuria and kidney pathology in spontaneously hypercholesterolaemic (SHC) rats, a rat chronic kidney disease (CKD) model. METHODS: SCO-792, an orally available enteropeptidase inhibitor, was administered [0.03% and 0.06% (w/w) in the diet] to 20-week-old SHC rats showing albuminuria and progressive decline in glomerular filtration rate (GFR) for five weeks. The effects of SCO-792 and the contribution of amino acids to these effects were evaluated. RESULTS: SCO-792 increased the faecal protein content, indicating that SCO-792 inhibited enteropeptidase in SHC rats. Chronic treatment with SCO-792 prevented GFR decline and suppressed albuminuria. Moreover, SCO-792 improved glomerulosclerosis and kidney fibrosis. Pair feeding with SCO-792 (0.06%) was less effective in preventing GFR decline, albuminuria and renal histological damage than SCO-792 treatment, indicating the enteropeptidase-inhibition-dependent therapeutic effects of SCO-792. SCO-792 did not affect the renal plasma flow, suggesting that its effect on GFR was mediated by an improvement in filtration fraction. Moreover, SCO-792 increased hydrogen sulphide production capacity, which has a role in tissue protection. Finally, methionine and cysteine supplementation to the diet abrogated SCO-792-induced therapeutic effects on albuminuria. CONCLUSIONS: SCO-792-mediated inhibition of enteropeptidase potently prevented GFR decline, albuminuria and kidney fibrosis; hence, it may have therapeutic potential against CKD.

Enteropeptidase inhibition improves kidney function in a rat model of diabetic kidney disease.

AIM: To examine the effects of an enteropeptidase inhibitor, SCO-792, on kidney function in rats. MATERIALS AND METHODS: The pharmacological effects of SCO-792 were evaluated in Wistar fatty (WF) rats, a rat model of diabetic kidney disease (DKD). RESULTS: Oral administration of SCO-792 increased faecal protein content and improved glycaemic control in WF rats. SCO-792 elicited a rapid decrease in urine albumin-to-creatinine ratio (UACR). SCO-792 also normalized glomerular hyperfiltration and decreased fibrosis, inflammation and tubular injury markers in the kidneys. However, pioglitazone-induced glycaemic improvement had no effect on kidney variables. Dietary supplementation of amino acids (AAs), which bypass the action of enteropeptidase inhibition, mitigated the effect of SCO-792 on UACR reduction, suggesting a pivotal role for enteropeptidase. Furthermore, autophagy activity in the glomerulus, which is impaired in DKD, was elevated in SCO-792-treated rats. Finally, a therapeutically additive effect on UACR reduction was observed with a combination of SCO-792 with irbesartan, an angiotensin II receptor blocker. CONCLUSIONS: This study is the first to demonstrate that enteropeptidase inhibition is effective in improving disease conditions in DKD. SCO-792-induced therapeutic efficacy is likely to be independent of glycaemic control and mediated by the regulation of AAs and autophagy. Taken together with a combination effect of irbesartan, SCO-792 may be a novel therapeutic option for patients with DKD.

Correction of the Lower Lip With a Cartilage Graft and Lip Resection in Patients With Facioscapulohumeral Muscular Dystrophy.

Facioscapulohumeral muscular dystrophy is an autosomal-dominant, slowly progressive myopathy that involves facial, shoulder, and upper arm muscles. Facial muscle atrophy and weakness leads to drooping of the lower lip, which has unfavorable functional and aesthetic outcomes. While there are several methods to correct drooping of the lower lip, including lip resection, free vascularized muscle transfer, and fascia suspension, there are no reports describing the use of an auricular cartilage graft to elevate the lip. The use of an auricular cartilage graft has several advantages, including a less invasive procedure and a longer-lasting effect. In this study, 3 patients with facioscapulohumeral muscular dystrophy underwent surgery involving an auricular cartilage graft with lip resection to sustain the lower lip, and satisfactory results were obtained. This procedure is simple and minimally invasive; thus, the authors believe that this is an appropriate technique to correct similar patients of lip deformity.

Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, ameliorates type 2 diabetes via reduced gluconeogenesis.

AIMS: Pyruvate dehydrogenase (PDH) catalyzes the decarboxylation of pyruvate to acetyl-CoA, which plays a key role in linking cytosolic glycolysis to mitochondria metabolism. PDH is physiologically inactivated by pyruvate dehydrogenase kinases (PDKs). Thus, activation of PDH via inhibiting PDK may lead to metabolic benefits. In the present study, we investigated the antidiabetic effect of PDK inhibition using dichloroacetate (DCA), a PDK inhibitor. MAIN METHODS: We evaluated the effect of single dose of DCA on plasma metabolic parameters in normal rats. Next, we investigated the antidiabetic effect of DCA in diabetic ob/ob mice. In addition, we performed in vitro assays to understand the effect and mechanism of action of DCA on gluconeogenesis in mouse myoblast cell line C2C12 and rat hepatoma cell line FaO. KEY FINDINGS: In normal rats, a single dose of DCA decreased the plasma level of pyruvate, the product of glycolysis, and the plasma glucose level only in the fasting state. Meanwhile, a single dose of DCA lowered the plasma glucose level, and a three-week treatment decreased the fructosamine level in diabetic ob/ob mice. In vitro experiments demonstrated concentration-dependent suppression of lactate production in C2C12 myotubes. In addition, DCA suppressed glucose production from pyruvate and lactate in FaO hepatoma cells. Thus, DCA-mediated restricted supply of gluconeogenic substrates from the muscle to liver, and direct suppression of hepatic gluconeogenesis might have contributed to its glucose-lowering effect in the current models. SIGNIFICANCE: PDK inhibitor may be considered as a potential antidiabetic agent harboring inhibitory effect on gluconeogenesis.

[A case of Paragonimus westermani with elevated FDG uptake into a pulmonary nodular lesion and right hilar and mediastinal lymph nodes on FDG-positron-emission tomography].

A 47-year-old Chinese woman living in Japan was referred with a 2-month history of cough with hemoptysis. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed increased FDG uptake into a pulmonary nodular lesion 25 mm in greatest dimension in the right upper lobe, and right hilar and mediastinal lymph nodes. Laboratory investigation did not reveal either eosinophilia or a marked elevation of serum IgE titer. A culture of bronchial lavage fluid was sterile and culture for mycobacteria was negative. Cytological examination results of transbronchial brushing samples were Class III. A partial resection of the right upper lobe was performed because of the possibility of primary lung cancer. Pathological examination of the nodular lesion showed helminthic eggs surrounded by dense inflammatory infiltrates, which mainly consisted of lymphocytes and eosinophils. Based on the findings of a serological study for helminth, the morphological characteristics of the eggs and the patient's history of eating raw crab, the patient was given a diagnosis of Paragonimus westermani, which can mimic primary lung cancer.

Sequential occurrence of microscopic polyangiitis and anti-glomerular basement membrane disease in a patient with small cell lung cancer: a case report.

BACKGROUND: The association between a preceding malignancy and the onset of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in several studies. While the co-existence of ANCA and anti-glomerular basement membrane (GBM) antibodies in an individual patient is not a common occurrence, this double-positive disease currently has no optimal treatment method. Herein, we report a case of a double-positive disease involving the sequential development of acute kidney injury (AKI) and diffuse alveolar hemorrhage (DAH) in a patient with small cell lung cancer (SCLC). CASE PRESENTATION: A 75-year-old Japanese woman was diagnosed with small cell lung cancer (cT3N2M1b cStage IV) and received chemotherapy. After one cycle of chemotherapy, she experienced fever and malaise. Her serum creatinine level rapidly increased, and she tested positive for myeloperoxidase (MPO)-ANCA and anti-GBM antibody. She was diagnosed with AKI due to microscopic polyangiitis (MPA) based on renal biopsy. Corticosteroid therapy was initiated, which improved her renal dysfunction. Eight days after she was discharged from the hospital, she complained of dyspnea and bloody sputum, and her condition rapidly progressed to respiratory failure. Upon chest imaging, ground-glass opacities were seen in her bilateral lower lungs. Laboratory examinations after admission revealed a lower MPO-ANCA titer and an elevated anti-GBM antibody titer compared to her previous admission. We diagnosed her with DAH due to an anti-GBM disease. After corticosteroid pulse therapy, plasma exchange was performed five times; her oxygen saturation and chest radiologic findings improved gradually. Following five cycles of plasma exchange, her oxygen saturation recovered to 95% in room air. CONCLUSIONS: To our knowledge, this is the first reported case of vasculitis caused by MPA and anti-GBM disease leading to the development of AKI and DAH during treatment of SCLC. SCLC, MPA, and anti-GBM disease may occur sequentially. A double-positive disease might have a worse prognosis; therefore, intensive therapy is more likely to achieve a better outcome.

[Interstitial pneumonitis caused by seasonal influenza vaccine].

A 74-year-old man who received seasonal influenza vaccination at a clinic developed fever and cough the following morning. He was referred to our hospital on the 5th day after vaccination because of bilateral pulmonary infiltration shadows on a chest X-ray film. Despite the administration of sulbactam/ampicillin and roxithromycin after admission, his symptoms did not improve. His bronchoalveolar lavage fluid (BALF) obtained by bronchoscopy on the 8th hospital day revealed a CD4/CD8 ratio of 6.8, 109 x 10(4)/ml, and 39% and 16% increases in lymphocyte fractions and eosinophil levels, respectively. Transbronchial lung biopsy showed organizing pneumonia. A drug-induced lymphocyte stimulation test (DLST) for seasonal influenza vaccine with BALF showed 210% of seasonal influenza (S.I). These results indicate that this vaccine caused pneumonitis with a hypersensitive reaction, according to drug-induced lung injury criteria.

[Therapeutic effect of omalizumab on 10 patients with severe persistent asthma].

BACKGROUND: Therapeutic effect of omalizumab was studied in Japanese patients with severe asthma. METHODS: Omalizumab was administered to 10 patients with bronchial asthma diagnosed as severe or very severe persistent asthma according to Asthma Prevention Management Guideline 2009, Japan (JGL 2009). Therapeutic efficacy was assessed 16 weeks after starting the treatment using Asthma Control Test (ACT), pulmonary function tests, and the peripheral eosinophil counts. In addition, number of acute exacerbation in 16-week period after starting the treatment was compared with that in 16-week period before the treatment and the previous year respectively. The questionnaire whether or not to continue omalizumab was conducted 16 weeks after starting the treatment. RESULTS: The total ACT score rose from 14.8 to 19.1 and peripheral eosinophil count decreased from 355.2 /microl to 209.8 /microl after starting the treatment. Peak expiratory flow and forced expiratory volume in one second also increased, though differences were insignificant. Number of acute exacerbation decreased from 3.0 times before the treatment and 2.4 times the same time last year to 1.3 times after starting the treatment. The result of the questionnaire revealed that patients wanted to discontinue because of financial burden, ambulant burden, and side effect, but no one responded to be ineffective. In fact, only the one discontinued omalizumab. CONCLUSION: Omalizumab produced improvement in subject symptoms and reduced acute exacerbation in patients with severe or very severe persistent asthma. The future challenge is to reduce financial and ambulant burden on patients.

Epidemiological evidence of multidrug-resistant Shigella sonnei colonization in India by sentinel surveillance in a Japanese quarantine station.

We applied a previously reported method to clarify whether a multidrug-resistant Shigella colonizes in a south Asian country. At Kansai Airport Quarantine Station, stool samples were collected from overseas travelers who reported a history of diarrhea. Shigella strains were isolated, ranging from 53 to 106 (average, 82.4) isolates/year (2001-2005), and almost 80% of the isolates were Shigella sonnei. The most frequent country of origin was India. Strains from the country of the most frequent origin were studied by antimicrobial susceptibility testing. Resistance to tetracycline, sulfamethoxazole-trimethoprim and nalidixic acid was observed at the highest frequency: in 23 of the 25 strains isolated in 2001, 5 of the 13 strains isolated in 2002, and 16 of the 19 strains isolated in 2005. Strains showing the most prevalent multidrug-resistance pattern were analyzed by pulsed-field gel electrophoresis (PFGE). The PFGE profiles showed that 27 of the 44 strains isolated in 2001, 2002, and 2005 were identical in PFGE pattern, as determined using two restriction enzymes. We concluded that a multidrug-resistant Shigella sonnei colonizes in a south Asian country.

Clinical impact of episodic nocturnal hypercapnia and its treatment with noninvasive positive pressure ventilation in patients with stable advanced COPD.

Purpose: Episodic nocturnal hypercapnia (eNH) caused by rapid eye movement (REM) sleep-related hypoventilation is often noted in patients with advanced COPD. The purpose of this study was to clarify the clinical significance of eNH and the effectiveness of eNH-targeted noninvasive positive pressure ventilation (NPPV). Patients and methods: We enrolled patients with stable, severe, or very severe COPD with daytime arterial partial oxygen pressure PaO2 ≥55 mmHg and daytime arterial partial carbon dioxide pressure PaCO2 <55 mmHg, who underwent overnight transcutaneous carbon dioxide pressure (PtcCO2) monitoring from April 2013 to April 2016. We retrospectively compared clinical characteristics, daytime blood gas analysis, frequency of exacerbation, serum albumin levels, and ratio of pulmonary artery to aorta diameter (PA:A ratio), between patients with COPD with and without eNH. For those with eNH, we applied NPPV and compared these clinical characteristics before and after NPPV. Results: Twenty-one patients were finally included in this study. Ten patients (47.6%) were evaluated to have eNH. These patients had lower albumin levels (p=0.027), larger PA:A ratio (p=0.019), and higher frequency of exacerbations during the last year (p=0.036). NPPV for the patients with eNH improved daytime PaCO2 compared with that 12 months after NPPV (p=0.011). The frequency of exacerbations 1 year before NPPV decreased 1 year after NPPV (p=0.030). Serum albumin levels improved 1 year after NPPV (p=0.001). Conclusion: In patients with stable severe or very severe COPD, eNH may be a risk factor of exacerbations, hypoalbuminemia, and pulmonary hypertension. NPPV may be effective against hypoalbuminemia and acute exacerbations. However, further study is necessary to validate these findings.

Relationship between limited joint mobility of the hand and diabetic foot risk in patients with type 2 diabetes.

BACKGROUND: Foot ulceration is a serious problem for patients with type 2 diabetes (T2D), and the early detection of risks for this condition is important to prevent complications. The present cross-sectional study in T2D patients determined the relationship between limited joint mobility (LJM) of the hand and diabetic foot risk classified using the criteria of the International Working Group on the Diabetic Foot (IWGDF). METHODS: Relationships between LJM of the hand and foot risk according to IWGDF category, HbA1c, age, body mass index, blood pressure, estimated glomerular filtration (eGFR), and diabetic complications (including diabetic peripheral neuropathy [DPN] and peripheral arterial disease [PAD]) were evaluated in 528 consecutive T2D patients. Poor glycemic control was defined as HbA1c ≥ 7%. RESULTS: Patients with LJM of the hand were older and had a longer duration of diabetes, a higher prevalence of diabetic complications, including DPN and PAD, and a higher IWDGF category (all P < 0.001). Multivariate logistic regression analysis revealed that the foot risk assessed with IWDGF category was correlated with age (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01-1.06; P = 0.001), poor glycemic control (OR 1.66; 95% CI 1.00-2.77; P = 0.04), eGFR (OR 0.98; 95% CI 0.97-0.99; P = 0.02), and the presence of LJM of the hand (OR 3.86; 95% CI 2.21-6.86; P < 0.001). CONCLUSIONS: The results demonstrate a correlation between LJM of the hand and foot risk. Diagnosis of diabetic hand is simple and non-invasive, and is thus a useful method for assessing the risk of diabetic foot in T2D patients.

Effectiveness of Shin'iseihaito in Asthmatic Patients with Upper Airway Diseases: A Retrospective Cohort Study.

BACKGROUND: Severe asthma is often associated with sinonasal diseases. Shin'iseihaito is a Japanese traditional herbal medicine, which is used to treat rhinosinusitis. However, its effectiveness in the treatment of asthma has not been elucidated. OBJECTIVE: The aims of this study were to examine the effectiveness of Shin'iseihaito in asthmatic patients with upper airway disease and to identify the characteristics of responders. METHODS: The medical records were retrospectively analyzed of asthmatic patients concomitant with upper airway disease in the outpatient department who had been administered Shin'iseihaito at least once from September 2011 to February 2015. They were classified into responders and non-responders, and the differences in characteristics were compared between the two groups. RESULTS: Shin'iseihaito was effective in 21/40 (52.5%) patients. There was no significant difference between responders and non-responders with regard to age, sex, or age of asthma onset. However, the frequency of aspirin intolerance, the treatment step of asthma, and serum immunoglobulin E levels were significantly higher in responders than they were in non-responders (p = 0.022, p = 0.017, and p = 0.017, respectively). The frequency of occurrence of concomitant eosinophilic chronic rhinosinusitis was not significantly different in both groups. CONCLUSION: Shin'iseihaito could be a potential alternative for the treatment of asthma in patients with upper airway diseases.

A very rare case of breast cancer in a female-to-male transsexual.

The incidence of breast cancer in female-to-male (FTM) transsexuals who received mastectomy and sex reassignment surgery is very rare. In fact, there is only one previous medical report of such a case. We experienced a case of an FTM transsexual who developed breast cancer 12 years after mastectomy and hysterectomy with bilateral salpingo-oophorectomy. Because he had been continuously receiving testosterone during the last 15 years and because histopathological examination revealed positive estrogen receptor and androgen receptor expression, we suggest that exogenous testosterone may have initiated the development of breast cancer via two distinct pathways. We describe the clinical course and condition of the patient and recommend that medical personnel consider the possibility of hormone-related cancer in FTM transsexuals receiving cross-sex hormones.

S-Mercuration of ubiquitin carboxyl-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells.

Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins. In this study, we identified proteins that undergo S-mercuration by MeHg. By combining two-dimensional SDS-PAGE, atomic absorption spectrometry and ultra performance liquid chromatography mass spectrometry (UPLC/MS/MS), we revealed that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a target for S-mercuration in human neuroblastoma SH-SY5Y cells exposed to MeHg (1 µM, 9 hr). The modification site of UCH-L1 by MeHg was Cys152, as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. MeHg was shown to inhibit the catalytic activity of recombinant human UCH-L1 in a concentration-dependent manner. Knockdown of UCH-L1 indicated that this enzyme plays a critical role in regulating mono-ubiquitin (monoUb) levels in SH-SY5Y cells and exposure of SH-SY5Y cells to MeHg caused a reduction in the level of monoUb in these cells. These observations suggest that UCH-L1 readily undergoes S-mercuration by MeHg through Cys152 and this covalent modification inhibits UCH-L1, leading to the potential disruption of the maintenance of cellular monoUb levels.

Ligation of human CD46 with purified complement C3b or F(ab')(2) of monoclonal antibodies enhances isoform-specific interferon gamma-dependent nitric oxide production in macrophages.

CD46, a complement regulatory protein widely expressed on human cells, serves as an entry receptor for measles virus (MV). We have previously shown that the expression of human CD46 in mouse macrophages restricts MV replication in these cells and enhances the production of nitric oxide (NO) in the presence of gamma interferon (IFN-gamma). In this study, we show that crosslinking human CD46 expressed on the mouse macrophage-like cell line RAW264.7 with purified C3b multimer but not monomer enhances NO production. The enhanced production of NO in response to IFN-gamma was observed again with C3b multimer but not monomer. The augmentation of NO production is human CD46-dependent with a CYT1>CYT2 profile. Thus, the reported MV-mediated NO production, irrespective of whether it is IFN-gamma-dependent or -independent, should be largely attributable to CD46 signaling but not to MV replication. Similar CYT1-dependent augmentation of NO production was reproducible with two CD46 ligating reagents, CD46-specific monoclonal antibodies (mAb) or their F(ab')(2) and MV hemagglutinin (H) and fusion (F) glycoproteins. Co-cultivation of mouse macrophages bearing human CD46 with Chinese hamster ovary (CHO) cells expressing MV H and F enhanced IFN-gamma-induced NO production. Yet, the NO levels induced by F(ab')(2) against CD46 or MV H/F on CHO cells were much lower than those induced by CD46-crosslinking mAb with Fc or MV infection. Removing the cytoplasmic tails of CD46 abrogated the augmentation of NO production triggered by all three stimulators. Thus, the CD46 CYT1 and CYT2 isoforms functionally diverge to elicit innate immune responses, which can be modulated by purified C3b multimer or anti-CD46 mAbs.

Accumulating microglia phagocytose injured neurons in hippocampal slice cultures: involvement of p38 MAP kinase.

In this study, microglial migration and phagocytosis were examined in mouse organotypic hippocampal slice cultures, which were treated with N-methyl-D-aspartate (NMDA) to selectively injure neuronal cells. Microglial cells were visualized by the expression of enhanced green fluorescent protein. Daily observation revealed microglial accumulation in the pyramidal cell layer, which peaked 5 to 6 days after NMDA treatment. Time-lapse imaging showed that microglia migrated to the pyramidal cell layer from adjacent and/or remote areas. There was no difference in the number of proliferating microglia between control and NMDA-treated slices in both the pyramidal cell layer and stratum radiatum, suggesting that microglial accumulation in the injured areas is mainly due to microglial migration, not to proliferation. Time-lapse imaging also showed that the injured neurons, which were visualized by propidium iodide (PI), disappeared just after being surrounded by microglia. Daily observation revealed that the intensity of PI fluorescence gradually attenuated, and this attenuation was suppressed by pretreatment with clodronate, a microglia toxin. These findings suggest that accumulating microglia phagocytosed injured neurons, and that PI fluorescence could be a useful indicator for microglial phagocytosis. Using this advantage to examine microglial phagocytosis in living slice cultures, we investigated the involvements of mitogen-activated protein (MAP) kinases in microglial accumulation and phagocytosis. p38 MAP kinase inhibitor SB203580, but not MAP kinase/extracellular signal-regulated kinase inhibitor PD98059 or c-Jun N-terminal kinase inhibitor SP600125, suppressed the attenuation of PI fluorescence. On the other hand, microglial accumulation in the injured areas was not inhibited by any of these inhibitors. These data suggest that p38 MAP kinase plays an important role in microglial phagocytosis of injured neurons.